Lecture 18: DNA Methylation & Histone Modification

Epigenetics

Heritable changes in gene activity and expression that occur without changes in DNA sequences.

Epigenomics

Genomes-wide analysis of epigenetic changes

What does the epigenetics landscape represent? 

How gene expression states can be stable yet changeable without DNA sequence change. 

What is the epigenome? 

The complete set of epigenetic modifications across the genome. 

What is DNA methylation?

The addition of a methyl group to cytosine (5th base)

What are CpG islands?

Regions with high frequency of CG dinucleotides; often found near promoters

What does '“p” in CpG  stand for? 

Phosphate bond between nucleotides on the same strand 

What are four key functions of DNA methylation?

Host defense, imprinting, X-chromosome inactivation, and chromatin stability

How does DNA methylation affect gene expression?

Usually represses transcription

What disease is linked to loss of maternal UBE3A? 

Angelman Syndrome 

What disease is linked to loss of paternal SNRPN?

Prader-Willi Syndrome

How is DNA methylation related to cancer?

Abnormal methylation can silence tumor suppressor genes

What is the gold standard for genome-wide DNA methylation profiling? 

Bisulfite sequencing 

What does bisulfite sequencing detect?

Methylated vs. unmethylated cytosines 

What is a histone octamer made of?

2 copies each of H2A, H2B, H3, and H4

What can histone tails undergo?

Various modifications like methylation and acetylation

What is the histone code?

Specific modifications on histones that regulate gene expression

What is histone mark ChIP-seq used for? 

Detecting location of histone modifications 

How does it differ from TF ChIP-seq?

Uses antibodies against modified histones instead of TFs.

What are super enhancers?

Clusters of enhancers with high TF/co-activating binding

What histone mark is associated with super enhancers? 

Broad H3K27ac signal 

Why are super enhancers important?

They regulate key cell identity and disease-related genes.